title: Longitudinal study of primary HIV-1 isolates in drug-naïve individuals reveals the emergence of variants sensitive to anti-HIV-1 monoclonal antibodies.
abstract: To study how virus evolution affects neutralization sensitivity and to determine changes that occur in and around epitopes, we tested the ability of 13 anti-HIV-1 gp120 (anti-V2, anti-V3, anti-CD4bd and anti-carbohydrate) human monoclonal antibodies (mAbs) to neutralize sequential viruses obtained from five HIV-1 chronically infected drug naïve individuals. Overall, primary viruses collected from patients at first visit were resistant to neutralization by all anti-HIV-1 mAbs with the exception of one virus sensitive to IgG1b12. Four of the five patients' viruses evolved increased sensitivity to neutralization by anti-V3 mAbs. Virus collected from a patient obtained 31 months later, evolved increased sensitivity to anti-V2, anti-V3, and anti-CD4bd mAbs. Furthermore, the anti-V2 and anti-CD4bd mAbs also exhibited increased neutralization capacities against virus collected from a patient 29 months later. Of the seven anti-V3 mAbs, five showed increased potency to neutralize the evolved virus from a patient collected after 11 months, and three exhibited increased potency against viruses from two patients collected 29 and 36 months later. Anti-V3 mAbs exhibited the most breadth and potency in neutralizing the evolving viruses. Sequence analysis of the envelope regions revealed amino acid conservation within the V3 loop, while most of the changes identified occurred outside the core epitopes and in particular within the C3 region; these may account for increased neutralization sensitivity. These studies demonstrate that in vivo, HIV-1 can evolve increased neutralization sensitivity to mAbs and that the spectrum of neutralization capacities by mAbs can be broader when studied in longitudinal analysis.
authors.affiliation: Department of Pathology, New York University School of Medicine, New York, New York, United States of America.
authors.forename: Bijayesh
authors.initials: B
authors.lastname: Haldar
authors.forename: Sherri
authors.initials: S
authors.lastname: Burda
authors.forename: Constance
authors.initials: C
authors.lastname: Williams
authors.forename: Leo
authors.initials: L
authors.lastname: Heyndrickx
authors.forename: Guido
authors.initials: G
authors.lastname: Vanham
authors.forename: Miroslaw K
authors.initials: MK
authors.lastname: Gorny
authors.forename: Phillipe
authors.initials: P
authors.lastname: Nyambi
mesh_terms: D000595:Amino Acid Sequence; D019380:Anti-HIV Agents / Q000276:immunology / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D024882:Drug Resistance, Viral / Q000187:drug effects* / Q000235:genetics / Q000276:immunology; D014644:Genetic Variation / Q000502:physiology; D015483:HIV Antibodies / Q000276:immunology / Q000494:pharmacology*; D015699:HIV Envelope Protein gp120 / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification*; D006801:Humans; D008137:Longitudinal Studies; D008969:Molecular Sequence Data; D020360:Neoadjuvant Therapy; D009500:Neutralization Tests; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D017386:Sequence Homology, Amino Acid
chemical_list: D019380:Anti-HIV Agents; D000911:Antibodies, Monoclonal; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D020033:Protein Isoforms